This proposal continues to study the kinetics and metabolism of mineralocorticoids and the control of renin release. Four general projects are considered. The first is to apply our recently published study of the origin of DOC from peripheral conversion of progesterone by 21 hydroxylation. Patients with adrenogenital syndrome or Cushing's Disease would appear from preliminary data to secrete from the adrenal considerable progesterone which may be a prehormone for DOC in the circulation. The remaining projects deal with control of renin release. In the 2nd project, we shall extend our recent observation that acute stimulati-n of renin release by converting enzyme inhibition (CEI) of angiotensin II feedback induces a reciprocal rise in active renin and reduction in inactive renin measured by acid or trypsin activation. In the proposed project we will compare the effect of CEI alone versus additional Beta adrenergic blockade or PG cyclooxygenase inhibition. Preliminary data suggests that PG's may act at a site different from adrenergic stimulation of renin release. Prostaglandins may act at the step involved in conversion of pro renin to renin and thus also be the key aspect of hyporeninemic hypoaldosteronism. The third and fourth projects will probe both in vitro (renal cortical slices) or in normal human subjects whether prostaglandins and angiotensin II act on inactive (pro) and active renin release through a calcium mechanism. Changes in extracellular calcium directly or calcium flux with ionophores (in vitro) will be used to make these observations. Our hypothesis in these studies is that angiotensin inhibits renin release by increasing and prostaglandins (vasodilators) stimulate pro greater than active renin release by reducing cellular calcium.